Effects of growth hormone on glucose metabolism and glucose transport in 3T3-F442A cells: dependence on cell differentiation.

Effects of growth hormone on glucose metabolism and glucose transport in 3T3-F442A cells: dependence on cell differentiation.
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DOI:
10.1210/endo-122-5-2247
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发表时间:
1988-05
期刊:
影响因子:
4.8
通讯作者:
J. Schwartz;C. Carter-Su
J. Schwartz;C. Carter-Su
中科院分区:
医学2区
文献类型:
--
作者:
J. Schwartz;C. Carter-Su

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在分化的3T3-F442A细胞系脂肪细胞中,与人生长激素孵育4小时可瞬间刺激葡萄糖氧化和脂质积累。当孵育延长至48小时,生长激素抑制这些指标的葡萄糖代谢。刺激葡萄糖氧化或脂质积累需要在生长激素孵育前一段时间的血清剥夺,而无论细胞是否被血清剥夺,生长激素的后期抑制作用都同样有效。由于3T3-F442A脂肪细胞在培养中从脂肪前细胞成纤维细胞分化,我们研究了分化状态对GH代谢反应的重要性。生长激素对前脂肪细胞成纤维细胞4或48小时后的葡萄糖氧化无重复性影响。为了确定生长激素对葡萄糖代谢的影响是否涉及葡萄糖转运的改变,我们在脂肪细胞中测量了低浓度(558 nM) [14C]葡萄糖的摄取。与GH孵育5-15分钟后,葡萄糖摄取增加2- 4倍。尽管GH持续存在,但这种快速反应在15-30分钟内达到顶峰,并在120分钟内消退。GH孵育24小时后,葡萄糖摄取被抑制。在前脂肪细胞中,生长激素偶尔会以一种短暂的方式刺激葡萄糖的摄取。当刺激存在时,通常比脂肪细胞的刺激幅度小,持续时间短。孵育24小时后,未观察到前脂肪细胞对葡萄糖摄取的抑制。与脂肪细胞相比,前脂肪细胞的反应性差异不能归因于受体结合的差异,也不能归因于GH受体类型或大小的可检测差异,这是由电泳凝胶中[125I]碘-人GH受体复合物的迁移决定的。这些发现表明生长激素迅速改变3T3-F442A脂肪细胞的葡萄糖摄取。葡萄糖摄取的变化很可能在先前观察到的gh诱导的葡萄糖转化为脂质和二氧化碳的变化中起主要作用。这些对生长激素的代谢反应依赖于3T3-F442A细胞的脂肪转化。由于3T3-F442A细胞表达脂肪细胞表型,GH代谢调节增加的发展似乎需要改变后结合或后受体现象。
In differentiated adipocytes of the 3T3-F442A cell line, 4-h incubation with human GH transiently stimulates glucose oxidation and lipid accumulation. When the incubation is extended to 48 h, hGH suppresses these indicators of glucose metabolism. The stimulation of glucose oxidation or lipid accumulation required a period of serum deprivation before incubation with GH, while the later inhibitory effect of GH occurred equally well whether or not cells were serum-deprived. Since the 3T3-F442A adipocytes differentiate in culture from preadipocyte fibroblasts, we examined the importance of the state of differentiation on metabolic responses to GH. GH had no reproducible effect on glucose oxidation after 4 or 48 h in the preadipocyte fibroblasts. To determine whether the effects of GH on glucose metabolism involved changes in glucose transport, the uptake of a low concentration (558 nM) of [14C]glucose was measured in the adipocytes. Glucose uptake increased 2- to 4-fold after 5-15 min of incubation with GH. This rapid response peaked in 15-30 min and subsided by 120 min despite the continued presence of GH. After 24 h of incubation with GH, glucose uptake was inhibited. In preadipocytes, GH occasionally stimulated glucose uptake in a transient manner. When present, the stimulation was generally of lesser magnitude and shorter duration than in the adipocytes. No inhibition of glucose uptake was observed in the preadipocytes after 24 h of incubation. These differences in responsiveness of the preadipocytes compared to the adipocytes cannot be attributed to differences in receptor binding or detectable differences in GH receptor type or size, as determined by migration of [125I]iodohuman GH-receptor complexes in electrophoretic gels. These findings indicate that GH rapidly alters glucose uptake in 3T3-F442A adipocytes. The changes in glucose uptake most likely play a major role in the GH-induced changes in the conversion of glucose to lipid and CO2 observed previously. These metabolic responses to GH are dependent on the adipose conversion of the 3T3-F442A cells. As the 3T3-F442A cells express the adipocyte phenotype, development of increased metabolic regulation by GH appears to require changes in postbinding or postreceptor phenomena.